Hepatitis

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Hepatitis Cirrhosis

• Dr. Gehan Mohamed Dr. Abdelaty Shawky

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Learning objectives

• Understand the normal Liver Functions so can
  predict what is the clinical picture when liver
  failure occur.
• Recognize definition of hepatitis and discuss its
  types(Acute, Chronic, Fulminant).
• List different Causes and Patterns of hepatitis
  .
• - Understand the differences between different
  types of viral hepatitis regarding Transmisson,
  Carrier state, Chronicity.
• List the cellular changes in both Acute and
  chronic Hepatitis.

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Learning objectives

• Understand difference between chronic hepatitis
  and fulminant hepatitis.
• Discuss definition ,etiology of cirrhosis and its
  variable gross pictures.
• discuss the Pathogenesis of Hepatic
  Encephalopathy.

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Hepatitis

• Definition
• Hepatitis is necro-inflammatory liver disease
  characterized by the presence of inflammatory
  cells in in the portal tracts then spillover to
  neighboring parynchmatous liver cells .

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Normal liver
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Hepatitis
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Causes of hepatitis

• 1. Viral hepatotropic (A, B, C, D.) and
  non-hepatotropic (cytomegalovirus and Epstein bar
  virus).
• 2. Alcoholic.
• 3. immune mediated autoimmune hepatitis.
• 4. Drug induced.
• 5. Metabolic disorders Hemochromatosis (due to
  iron accumulation) and Wilsons disease (copper
  accumulation) can cause liver inflammation and
  necrosis.

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• 6. Other causes
• Biliary obstruction by gall stones .
• ischemic hepatitis associating shock.
• giant cell hepatitis ,common in children may be
  due to viral infection.

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Virus Hep-A Hep-B Hep-C
agent RNA DNA RNA
Transmisson. Feco-oral Parenteral -maternal to fetal -sexual -drug abusers - Parenteral maternal to fetal Sexual drug abusers
Carrier state None 0.1-1.0 0.2-1.0
Chronic Hepatitis None 5-10 gt50
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Patterns of hepatitis

• Carrier state is an individual who harbor and
  can transmit the virus but has no manifest
  symptoms.
• Acute hepatitis hepatitis is considered acute
  if its manifestation persist for period less than
  six months.
• Chronic hepatitis hepatitis is considered
  chronic if there is clinical or seriological
  evidence of liver pathology persistent for more
  than six consequent months.
• Fulminant hepatitis hepatitis is considered
  fulminant if massive hepatic cell necrosis
  happened within few weeks leading to acute
  hepatic failure and hepatic encephalopathy.

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Acute Viral Hepatitis
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Diagnosis of acute hepatitis

• 1. Clinical picture.
• 2. Laboratory investigations.
• 3. Histopathologic diagnosis of liver biopsy.

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1. Clinical picture of acute viral hepatitis
(AVH)

• AVH is more likely to be asymptomatic in younger
  people.
• If AVH is symptomatic, it may be either non
  specific or specific symptoms.
• Initial features are of nonspecific flu-like
  symptoms include malaise, muscle and joint aches,
  fever, nausea or vomiting, diarrhea, loss of
  appetite, and headache.
• More specific symptoms and signs are yellow
  color of the eyes and skin (i.e., jaundice) and
  abdominal discomfort from hepatomegaly (swelling
  of the liver).

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jaundice
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2. Laboratory investigations of AVH

• 1. Ultrasound examination to detect any biliary
  stones, hepatomegaly.
• 2. Serologic examination to detect
• a- Elevated hepatic enzymes as
• - aspartate aminotransferase(AST)
• - alanine aminotransferase(ALT).
• b- Viral hepatitis markers as HBV sAg, HCV
  Antigen and Antibody
• c- Autoantibodies as in case of autoimmune
  hepatitis.
• d- Polymerase chain reaction(PCR) to identify
  the virus.

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3. Histopathology of AVH

• The normal liver architecture is usually
  preserved.
• Inflammatory cellular infiltrate (plasma cells,
  lymphocytes and neutrophils) inside portal tracts
  and around foci of necrosis.
• The hepatocytes show
• Apoptosis the cells appear acidophilic
  (Councilman bodies).
• Hydropic degeneration.
• Cholestasis means accumulation of bile in liver
  cells even canalicular bile plugs can be formed
  in cases of hepatitis caused by biliary
  obstruction by stones.
• Hepatocyte regeneration.

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Acute - Hepatitis - Chronic
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Liver Biopsy Chronic Hepatitis the
inflammatory cells are present in portal tract
and in periportal areas
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Councilman bodies are eosinophilic dead apoptotic
liver cells
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Cholestasis accumlation of bile inside
hepatocytes
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Chronic hepatitis
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Clinical picture of Chronic hepatitis

• Often no symptoms at all.
• It is commonly identified on blood tests
  performed either for screening or to evaluate
  nonspecific symptoms.
• nonspecific symptoms such as malaise, tiredness
  and weakness.
• The occurrence of jaundice indicates advanced
  liver damage.
• On physical examination there may be enlargement
  of the liver

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Histopathology for chronic hepatitis

• I. Portal tracts show
• a. Piece meal necrosis necrosis of the
  hepatocytes at the limiting plate.
• b. Portal tract inflammation
• mononuclear inflammatory cells lymphocytes,
  macrophages with occasional plasma cells.
• Lymphoid follicle formation (with HCV).
• Bile duct inflammation (with HCV).

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• II. The hepatic lobules show
• Degeneration Fatty change (with HCV).
• Necrosis
• Focal (spotty) necrosis surrounded by
  inflammatory cells.
• Confluent necrosis and bridging necrosis with
  progressive hepatitis.
• Dysplasia of hepatocytes (precancerous).
• Von Kupffer cell hyperplasia.

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• Specific diagnostic lesions
• Ground glass appearance of hepatocytes (with
  HBV).
• Presence of cupper particles inside the
  hepatocytes (with Wilson disease).
• Rosseting occasional arrangement of a group of
  hepatocytes around a central bile canaliculus.
  Characteristic of auto-immune hepatitis.
• III. Fibrosis Cirrhosis.

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• Grading of chronic hepatitis by assessing the
  degree of activity this is done by examining 4
  parameters portal inflammation, piece meal
  necrosis, focal (spotty) necrosis and confluent
  necrosis. The degree of activity is graded as
  mild, moderate and marked according to the score
  of these parameters.
• Staging of chronic hepatitis by assessment of the
  degree of fibrosis

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chronic hepatitis with piece meal necrosis
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Histopathology show ground glass hepatocytes,
which are seen in chronic hepatitis B infections
represent accumulations of viral antigen in the
endoplasmic reticulum. HE
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Histopathology show lymphoid aggregates and
fatty change of the hepatocytes, which are
characteristically seen in chronic hepatitis C
infections
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Liver cirrhosis
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Definition

• Chronic Diffuse, irreversible disorder of the
  liver characterized by
• Liver cell degeneration and necrosis.
• Replaced by extensive fibrosis .
• Compensatory hyperplasia of the remaining healthy
  liver cells leading to the formation of the
  Regenerating parenchymal nodules.
• Complete loss of normal architecture.

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Etiological classification of Cirrhosis

• A. Congenital cirrhosis
• Congenital syphilis.
• Hemochromatosis.
• Glycogen storage disease.
• Wilson disease.
• a1 antitrypsin deficiency.

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• B. Acquired cirrhosis
• 1. Post-hepatitic (viral).
• 2. Alcoholic.
• 3. Biliary cirrhosis.
• 4. Cirrhosis caused by circulatory disorders e.g.
  chronic right sided heart failure.

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Complications of Cirrhosis

• 1. Liver cell Failure
• 2. Portal hypertension
• 3. Hepatocellular carcinoma.

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Normal Liver
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Micronodular cirrhosis
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Macronodular Cirrhosis
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Normal Liver Histology
CV
PT
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Liver Biopsy Cirrhosis
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Liver Biopsy Cirrhosis
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Liver cell failure
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Normal Liver Functions

• Metabolism Carbohydrate, Fat Protein.
• Secretory bile, Bile acids, salts.
• Excretory Bilirubin, drugs, toxins.
• Synthesis Albumin, coagulation factors.
• Storage Vitamins, carbohydrates etc.
• Detoxification toxins, ammonia, etc.

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Manifestations of liver cell failure

• 1. Jaundice yellow colour of skin ,mucosa due to
  hyperbilirubinemia as liver became unable to
  conjugate bilirubin so it not secreted in urine
  and so it is reabsorbed by blood and precipitate
  in tissues.
• 2. Coagulopathy? bleeding tendency
• 3. Hypoproteinemia specially albumin ? decrease
  osmotic pressure of blood ? generalized edema
• .

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• 4. Hepatic Encephalopathy caused by the
  inability of the liver to detoxify amonia which
  produced by effect of intestinal bacteria on food
  so this amonia can affect brain causing coma.
• 5. Hyperestrogenemia due to decrease estrogen
  degradation by the diseased liver leading to
  gynaecomastia and testicular atrophy in males

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Gynaecomastia in cirrhosis i.e. enlargement of
male breast due to failure of degradation of
estrogen by the diseased liver.
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Portal hypertension
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• Portal hypertension leading to
• 1. Varices esophageal varices, piles.
• 2. Splenomegaly due to splenic congestion.
• 3. Ascites which is accumulation of transudate
  in the peritoneal cavity.

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Ascitis in Cirrhosis
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CirrhosisClinical Features
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Thanks